Evidence map›Paper›PMID 42545212›Full record

ArticleThe Biochemical journal2026

The role of CYP3A-CYP2E1 interactions in activation of CYP3A enzymes by chronic alcohol exposure.

Dmitri R Davydov, Kannapiran Ponraj, Nadezhda Y Davydova, Guihua Yue, Dilip Kumar Singh, Arpita Guha Neogi, Kari A Gaither, Bhagwat Prasad

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Article in The Biochemical journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Dmitri R DavydovDepartment of Chemistry, Washington State University, Pullman, WA 99164, U.S.A.ORCID 0000-0001-8520-0033
Kannapiran PonrajDepartment of Chemistry, Washington State University, Pullman, WA 99164, U.S.A.ORCID 0000-0002-7195-5432
Nadezhda Y DavydovaDepartment of Chemistry, Washington State University, Pullman, WA 99164, U.S.A.
Guihua YueDepartment of Pharmaceutical Sciences, Washington State University, Spokane, WA 99202, U.S.A.
Dilip Kumar SinghDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, U.S.A.ORCID 0000-0001-7248-6714
Arpita Guha NeogiDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, U.S.A.
Kari A GaitherDepartment of Chemistry, Washington State University, Pullman, WA 99164, U.S.A.ORCID 0000-0003-2014-4362
Bhagwat PrasadDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, U.S.A.ORCID 0000-0002-9090-0912

Funding

Inter-Enzyme Crosstalk in the Cytochrome P450 Ensemble: Implications for the Effects of Alcohol on Drug Metabolism and Alcohol-Drug InteractionsR01AA030155 · NIAAA · WASHINGTON STATE UNIVERSITY · PI DAVYDOV, DMITRI R, PRASAD, BHAGWAT · 2022 to 2025
$2.0M
HHS | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) R01AA030155
6 · The paper itself

Abstract

To examine the effect of chronic alcohol exposure on the activity of CYP3A enzymes in human liver, we studied the metabolism of CYP3A-specific substrates 7-benzyloxyquinoline (7-BQ) and ivermectin in 23 preparations of human liver microsomes (HLM) obtained from donors with documented alcohol exposure, from non-drinkers to heavy alcoholics. All HLM samples were characterized for the composition of the cytochrome P450 pool by global proteomics. Our studies revealed a significant increase in the activities of CYP3A enzymes by alcohol exposure. This effect is not associated with CYP3A enzyme levels, which do not correlate with alcohol exposure. Instead, the rates of 7-BQ and ivermectin metabolism correlate with the content of alcohol-inducible CYP2E1. However, this enzyme does not metabolize ivermectin, and its activity with 7-BQ is negligible. A significant increase in the rate of ivermectin demethylation was also observed in CYP3A4-containing Supersomes® and pooled HLM upon incorporation of purified CYP2E1 into their membrane. These results suggest that the reported acceleration of the elimination of drugs metabolized by CYP3A enzymes by alcohol exposure is due to functional effects of the interaction between CYP3A and CYP2E1. To elucidate the potential mechanism of this effect, we studied the formation of CYP2E1-CYP3A4 complexes in CYP3A4-containing Supersomes with co-incorporated CYP2E1 using tag-transfer chemical crosslinking mass spectrometry (CX-MS). These experiments confirmed physical interactions between the proteins and allowed the identification of CYP3A4 residues at the sites of contact. This information was used to build structural models of the CYP2E1-CYP3A4 complex and to propose possible mechanisms for the observed effects.

Indexed as

AlcoholismCytochrome P-450 CYP2E1Cytochrome P-450 CYP3AEthanolEnzyme ActivationHumansIvermectinMicrosomes, LiverCytochrome P-450 CYP2E1Cytochrome P-450 CYP3AEthanolIvermectinCYP2E1CYP3A4cytochrome p450drug metabolismprotein cross-linkingprotein-protein interactions

Identifiers

PMID42545212

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.